Cytotoxic activity of violacein in human colon cancer cells

Carvalho, D; Costa, Fábio T. M.; Durán, Nelsón; Haun, Marcela

doi:10.1016/j.tiv.2006.06.007

Cited by 91 publications

(77 citation statements)

References 27 publications

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“…4). Similarly, mutation of either Tyr 17 or Ser 19 , each between 3 and 5 Å from the bound PEG molecule (Fig. 3C) resulted in a significant decrease in prodeoxyviolacein 3 production (Fig.…”

Section: Resultsmentioning

confidence: 83%

“…By contrast, mutation of Cys 35 , ϳ4 Å from the bound PEG molecule (Fig. 3C), yet on a different side of the PEG from Tyr 17 and Ser 19 , did not result in a significant change in prodeoxyviolacein 3 production (Fig. 4).…”

Section: Resultsmentioning

confidence: 91%

“…Our site-directed mutagenesis studies have identified a number of residues likely to be involved in binding polar parts of the substrate molecule or in catalysis: Tyr 17 , Ser 19 , Asn 51 , Glu 66 , and Arg 172 . Although mutation of any of these residues does not completely abolish VioE activity, the significant decrease in activity by each of these mutants implies that they play a role in enzymatic acceleration of prodeoxyviolacein 3 production by VioE.…”

Section: Discussionmentioning

confidence: 99%

“…1) is a purple pigment that gives tropical bacterium Chromobacterium violaceum its characteristic coloring (1-5). Violacein 5 has potential medical applications as an antibacterial (6 -8), anti-tryptanocidal (8 -10), anti-ulcerogenic (11), and anti-cancer drug (8,(12)(13)(14)(15)(16)(17). The molecule, made of L-tryptophan and molecular oxygen (18 -21), was originally thought to be synthesized by the action of just four enzymes VioABCD (22, 23), but an additional open reading frame (24), also in the operon, was shown to encode the enzyme VioE (25, 26).…”

mentioning

confidence: 99%

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The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

Ryan

Balibar

Turo

et al. 2008

Journal of Biological Chemistry

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VioE, an unusual enzyme with no characterized homologues, plays a key role in the biosynthesis of violacein, a purple pigment with antibacterial and cytotoxic properties. Without bound cofactors or metals, VioE, from the bacterium Chromobacterium violaceum, mediates a 1,2 shift of an indole ring and oxidative chemistry to generate prodeoxyviolacein, a precursor to violacein. Our 1.21 Å resolution structure of VioE shows that the enzyme shares a core fold previously described for lipoprotein transporter proteins LolA and LolB. For both LolB and VioE, a bound polyethylene glycol molecule suggests the location of the binding and/or active site of the protein. Mutations of residues near the bound polyethylene glycol molecule in VioE have identified the active site and five residues important for binding or catalysis. This structural and mutagenesis study suggests that VioE acts as a catalytic chaperone, using a fold previously associated with lipoprotein transporters to catalyze the production of its prodeoxyviolacein product.Violacein 5 (Fig. 1) is a purple pigment that gives tropical bacterium Chromobacterium violaceum its characteristic coloring (1-5). Violacein 5 has potential medical applications as an antibacterial (6 -8), anti-tryptanocidal (8 -10), anti-ulcerogenic (11), and anti-cancer drug (8,(12)(13)(14)(15)(16)(17). The molecule, made of L-tryptophan and molecular oxygen (18 -21), was originally thought to be synthesized by the action of just four enzymes VioABCD (22, 23), but an additional open reading frame (24), also in the operon, was shown to encode the enzyme VioE (25, 26). A 22-kDa protein with few homologues based on sequence analysis, VioE is required for formation of prodeoxyviolacein 3, a precursor to violacein 5 (25-27). Without the presence of VioE, a shunt product, chromopyrrolic acid 4, is produced, rather than 3 (25-27). VioE is therefore required for the 1,2 shift of the indole ring and subsequent chemistry that gives violacein 5 its distinctive architecture. Surprisingly, despite carrying out this chemistry, VioE lacks any bound cofactors or metal ions (26).Using genetic and biochemical analysis, an enzymatic pathway for violacein 5 production has been determined ( Fig. 1), and intermediates have been identified (26), with the major exception that the substrate of VioE (product of VioB) is still unknown. It has, however, been established that the product of VioB is the substrate for VioE; when VioA and VioB are incubated in a reaction mixture with the VioA substrate L-tryptophan for 10 min, passed through a 10-kDa filter (removing VioA and VioB), and then incubated with VioE, prodeoxyviolacein 3 is produced (26). By contrast, in the absence of VioE, no prodeoxyviolacein 3 is made (26). This result reveals three things: first, the VioB product is a small molecule that can pass through a 10-kDa filter; second, no interaction between VioB and VioE is necessary for product formation; and third, VioE is a catalyst. The small molecule passed through the filter (the product of VioB and substra...

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Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

Ryan

Balibar

Turo

et al. 2008

Journal of Biological Chemistry

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“…It is known that violacein is a potent apoptosis inducer in leukemic HL-60 lineage by tumoral necrosis factor 1, caspase-8 and MAP-kinase p38 activation. 21 This drug is also capable of inducing cell death by generalized oxidative stress in colorectal tumoral lineage HT-29 22 and direct enzyme modulation in lymphocytes. 23 Despite its therapeutic potential, violacein exhibits poor water-solubility, which restricts its use in vivo.…”

Section: Dovepressmentioning

confidence: 99%

Antitumoral activity of L-ascorbic acid-poly-D,L-(lactide-co-glycolide) nanoparticles containing violacein

Martins

Frungillo²,

Anazzetti³

et al. 2010

IJN

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It has been demonstrated that tumoral cells have a higher uptake of ascorbic acid compared to normal cells. This differential characteristic can be used as a way to improve the specificity of antitumoral compounds if combined with polymeric drug delivery systems. The aim of this study was to prepare, characterize and evaluate the antitumoral activity of poly-D,L-(lactide-co-glycolide) 50:50 loading the antitumoral compound violacein and capped with L-ascorbic acid. Nanoparticles were prepared using the nanoprecipitation method and morphologically characterized by scanning electron microscopy (SEM). The average diameter and Zeta potential were determined by photon correlation spectroscopy method (PCS), and assays were carried out to determine the content of ascorbic acid and in vitro drug release kinetics. The antitumoral activity of this system was also evaluated against HL-60 cells by tetrazolium reduction assay. Nanoparticles with size distribution between 300-400 nm and strong negative outer surface (-40 mV) were obtained by this method. Analysis of ascorbic acid content showed that this compound was mainly localized on the external surface of nanoparticles. Violacein loading efficiency was determined as 32% ± 1% and this drug was gradually released from nanoparticles at different rates depending on the composition of the release media. In addition, this system was observed to be 2 × more efficient as an antitumoral compared with free violacein.

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Violacein and Prodiginines from Marine Bacteria

Enomoto

2020

Encyclopedia of Marine Biotechnology

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Cytotoxic activity of violacein in human colon cancer cells

Cited by 91 publications

References 27 publications

The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins

Antitumoral activity of L-ascorbic acid-poly-D,L-(lactide-co-glycolide) nanoparticles containing violacein

Violacein and Prodiginines from Marine Bacteria

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